A substance that stimulates the secretion of the follicle stimulating hormone has been reported by many investigators. This substance is present in homogenates of hypothalamic tissue from many species. The hypothalamus is a part of the forebrain; prosencephalon, which unlike the cerebellum and crebral hemispheres, has maintained a relative constancy of arrangement throughout its phylogenetic history. The hypothalamus is a small section of tissue of the diencephalon which is the posterior part of the prosencephalon, consisting of the hypothalamus, thalamus, metathalamus, and epithalamus. The hypothalamus is not considered as an organ with boundaries, but rather as a region of brain tissue which has significant functions in many aspects of mammalian physiology. Basically, the hypothalamus is divisible into medial and lateral portions. The medial portion joins the third ventricle. The lateral portion contains cells that are diffusely arranged among the fibers of what has long been called the medial forebrain bundle. An anatomic relationship which is a constant feature of the hypothalamus is its intimate association with the pituitary gland. The pituitary or hypophysis consists of anterior and posterior lobes, and the pars intermedia. Biochemical transport of the neurohormones from the hypothalamus to the anterior lobe or adenohypophysis is provided by certain blood vessels in a portal system which is a network of capillaries. The blood in these capillaries passes down the pituitary stalk and becomes distributed through another system of capillaries in the anterior lobe and one of the neurohormones thus transported is folliculotropin releasing hormone (FRH).
It is generally considered that there is one hypothalamic releasing hormone for each anterior pituitary hormone. This concept has not been proven and it has been found that the known luteotropin releasing hormone (LRH) and thyrotropin releasing hormone (TRH) stimulate the release of two pituitary hormones. It has been found that TRH can stimulate the release of prolactin and thyrotropin and that LRH can stimulate the release of luteotropin and folliculotropin.
A prolactin releasing hormone (PRH) has recently been described as being chemically distinct from TRH. [Valverde-R., et al., Endocrinology, 91, 982 (1972)]. We now describe the biosynthesis of a Folliculotropin Releasing Hormone (FRH) chemically separable from LRH.
It has been proposed by Schally and White [Schally, et al., Science, 173, 1036 (1971) and White, Hypophysiotropic Hormones of the Hypothalamus, J. Meites, ed., p. 248, 1970] that luteotropin releasing hormone (LRH) is the natural regulator of both luteotropin and folliculotropin. More recently, [Guillemin and Burgus, Scientific American, 227, 24 (1972)] it has been stated by noted investigators that "A third gonadotropic hormone, FSH (follicle stimulating hormone), may have its own hypothalamic releasing factor, FRF, but that has not been demonstrated."
We have found, indeed, that LRH releases folliculotropin to a limited degree in addition to a potent release of luteotropin. More important is our finding that hypothalamic extracts contain a hormone, chemically distinct from LRH, that stimulates a very high level of folliculotropin release as well as a limited release of luteotropin. The functions of the gonads are thus controlled by two hypothalamic releasing hormones, LRH and FRH, that both regulate the release of luteotropin and folliculotropin from the anterior pituitary. Each releasing hormone appears to have a primary and a secondary regulatory activity.
Only a few nanograms of each releasing hormone appears to exist in the hypothalamus of a single animal. Therefore, hypothalami from thousands of animals are required to isolate a sufficient quantity for structure elucidation studies. The biosynthetic approach to the isolation of a new hormone makes it possible to attach a radioactive tag to the compound of interest and increase the amount of hormone present in the starting tissue. Once the hypothalamic hormone has been radioactively labeled, it can be added to a large amount of tissue. This process increases the total quantity of hormone present to a quantity suitable for structure elucidation after the necessary purification procedures.